We are investigating the molecular and cellular basis for the autoimmune response to erythrocyte membrane antigens, utilizing as the disease model the spontaneous autoimmune hemolytic anemia of NZB mice. We are attempting to identify the cellular interactions and cellular basis at the B-lymphocyte and T-lymphocyte levels for this response. The means by which autoimmunocompetent B lymphocytes are normally controlled and suppressed are being identified; and the aberrations in control which culminate in derepression of autoimmuno-competent B lymphocytes and the synthesis of autoantibody are being elucidated. The role of thymus-derived lymphocytes, viruses, and genetic endowment on these control parameters are the focus of current studies.